The chemistry and interactions of the complement (C) attack proteins (C5-C9) are reasonably well defined, but the control of this powerful biological effector system is much less well understood. It is the aim of this proposal to approach the study of control of the C attack system from two different aspects. First, studies on the inhibition of the action of the C567 complex by serum proteins will be continued. The two or three major non-lipoprotein substances which inhibit this part of the C sequence will be isolated, characterized, and their mechanism of action determined using purified, radiolabeled C components. Secondly the mechanisms by which nucleated cells resist C attack will be examined. Using labeled C7, the fate of C567 complexes bound to lymphoblastoid cells will be followed. Clearance of complexes from normal or metabolically inhibited cells will be correlated with the ability of the C attack proteins to kill the cells. The effects of membrane-bound antibody or C3b on the susceptibility of nucleated cells to C-mediated cytotoxicity will be quantitatively assessed, and correlated with the specific binding of labeled C components to the target cell. This study represents the first investigation into the interaction between the isolated human C attack proteins and human nucleated cells and as such, may produce fundamental new information on the role of the complement attack mechanism in the destruction of tumor cells.